The frequency and intensity of harmful algal blooms (HABs) and phytoplankton community shifts toward toxic species have increased worldwide. Although most research has focused on eutrophication as the cause of this trend, many other global-and regional-scale anthropogenic influences may also play a role. Ocean acidification (high pCO 2 /low pH), greenhouse warming, shifts in nutrient availability, ratios, and speciation, changing exposure to solar irradiance, and altered salinity all have the potential to profoundly affect the growth and toxicity of these phytoplankton. Except for ocean acidification, the effects of these individual factors on harmful algae have been studied extensively. In this review, we summarize our understanding of the influence of each of these single factors on the physiological properties of important marine HAB groups. We then examine the much more limited literature on how rising CO 2 together with these other concurrent environmental changes may affect these organisms, including what is possibly the most critical property of many species: toxin production. New work with several diatom and dinoflagellate species suggests that ocean acidification combined with nutrient limitation or temperature changes may dramatically increase the toxicity of some harmful groups. This observation underscores the need for more in-depth consideration of poorly understood interactions between multiple global change variables on HAB physiology and ecology. A key limitation of global change experiments is that they typically span only a few algal generations, making it difficult to predict whether they reflect likely future decadal-or century-scale trends. We conclude by calling for thoughtfully designed experiments and observations that include adequate consideration of complex multivariate interactive effects on the long-term responses of HABs to a rapidly changing future marine environment.