The purpose of modern industrial herbicides is to control weeds. The species of weeds that plague crops today are a consequence of the historical past, being related to the history of the evolution of crops and farming practices. Chemical weed control began over a century ago with inorganic compounds and transitioned to the age of organic herbicides. Targeted herbicide research has created a steady stream of successful products. However, safeners have proven to be more difficult to find. Once found, the mode of action of the safener must be determined, partly to help in the discovery of further compounds within the same class. However, mounting regulatory and economic pressure has changed the industry completely, making it harder to find a successful herbicide. Herbicide resistance has also become a major problem, increasing the difficulty of controlling weeds. As a result, the development of new molecules has become a rare event today.

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In response to changing market dynamics, the discovery of new herbicides has declined significantly over the past few decades and has only seen a modest upsurge in recent years. Nevertheless, the few introductions have proven to be interesting and have brought useful innovation to the market. In addition, herbicide-tolerant or herbicide-resistant crop technologies have allowed the use of existing nonselective herbicides to be extended into crops. An increasing and now major challenge is being posed by the inexorable increase in biotypes of weeds that are resistant to herbicides. This problem is now at a level that threatens future agricultural productivity and needs to be better understood. If herbicides are to remain sustainable, then it is a must that we adopt diversity in crop rotation and herbicide use as well as increase the use of nonchemical measures to control weeds. Nevertheless, despite the difficulties posed by resistant weeds and increased regulatory hurdles, new screening tools promise to provide an upsurge of potential herbicide leads. Our industry urgently needs to supply agriculture with new, effective resistance-breaking herbicides along with strategies to sustain their utility.Only a few companies are significantly pursuing herbicide discovery in the 21st century. Most of these have combined seed and traits businesses, since fees for traits constitute a considerable part of the income of agrochemical companies today. In concert with a review of the historical perspectives of herbicide research (Kraehmer et al., 2014), we provide here a short description of the current major research activities within the remaining 21st century agrochemical companies. After an overview of the chemicals that have entered the market in the 21st century, we provide a brief summary of the current nature of the weed-resistant herbicide problem. We then go on to summarize breedingassisted and transgenic approaches toward the improvement of crop selectivity through the delivery of so-called herbicide-tolerant (HT) or herbicide-resistant crops, and conclude with a discussion of the new herbicide discovery screening tools that have been employed since the year 2000 and prospects for the future. MAJOR CHEMICAL TRENDS AFTER 2000Several new compounds have entered the herbicide market in recent years. Although not representing new modes of action (MoAs), they have increased the number of tools available for farmers to use to control weeds. Even in known and older herbicidal classes, new, interesting, and marketable molecules have been discovered. For example, and perhaps surprising given the relative age of the class of herbicides, new (after 2000) acetolactate synthase (ALS) inhibitors have provided solutions for farmers that can be regarded as real innovations. One of them is mesosulfuron-methyl (Fig. 1), a sulfonylurea herbicide that, when combined with iodosulfuron-methyl sodium, has broad-spectrum postemergence grass weed control at dose rates of 4.5 to 15 g active ingredient (a.i.) ha 21 (Safferling, 2005). Another ...

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