The transition from micro well plate and robotics based high throughput screening (HTS) to chip based screening has already started. This transition promises reduced droplet volumes thereby decreasing the amount of fluids used in these studies. Moreover, it significantly boosts throughput allowing screening to keep pace with the overwhelming number of molecular targets being discovered. In this review, we analyse state-of-the-art droplet control technologies that exhibit potential to be used in this new generation of screening devices. Since these systems are enclosed and usually planar, even some of the straightforward methods used in traditional HTS such as pipetting and reading can prove challenging to replicate in microfluidic high throughput screening (μHTS). We critically review the technologies developed for this purpose in depth, describing the underlying physics and discussing the future outlooks.