The advent of microfluidics in the 1990s promised a revolution in multiple industries, from healthcare to chemical processing. Deterministic Lateral Displacement (DLD) is a continuous-flow microfluidic particle separation method discovered in 2004 that has been applied successfully and widely to the separation of blood cells, yeast, spores, bacteria, viruses, DNA, droplets, and more. DLD is conceptually simple and can deliver consistent performance over a wide range of flow rates and particle concentrations.Despite wide use and in-depth study, DLD has not yet been fully understood or fully optimised, with different approaches to the same problem yielding varying results. We endeavour here to provide an up-to-date expert opinion on the state-of-art and current fundamental, practical, and commercial challenges as well as experimental and modelling opportunities. Since these challenges and opportunities arise from constraints on hydrodynamics, fabrication and operation at the micro-and nano-scale, we expect this article to serve as a guide for the broader micro-and nanofluidic community to identify and address open questions in the field.