The conformational flexibility of protein targets is being increasingly recognized in the drug discovery and design processes. When working on a particular disease-related biochemical pathway, it is of crucial importance to carefully select druggable protein binding pockets among all those cavities that may appear transiently or permanently on the respective protein surface. In this review, we will focus on the conformational dynamics of proteins that governs the formation and disappearance of such transient pockets on protein surfaces. We will also touch on the issue of druggability of transiently formed pockets. For example, protein cavities suitable to bind small drug-like molecules show an increased pocket size and buriedness when compared to empty sites. Interestingly, we observed in molecular dynamics simulations of five different protein systems that the conformational transitions on the protein surface occur almost barrierless and large pockets are found at similar frequencies as small pockets, see below. Thus, the dynamical processes at protein surfaces are better visualized as fluid-like motion than as energetically activated events. We conclude by comparing two computational tools, EPOS and MDpocket, for identifying transient pockets in PDK1 kinase. We illustrate how the obtained results depend on the way in which corresponding pockets in different molecular dynamics snapshots are connected to each other.