Proteins are not static objects. To carry out their functions in the cells and participate in biochemical interaction networks, proteins have to explore different conformational substates, which favor the adaptation to different partners and ultimately allow them to respond to changes in the environment. In this paper we discuss the implications of including the atomistic description of protein dynamics and flexibility in the context of drug discovery and design. The underlying idea is that a better understanding of the atomistic details of molecular recognition phenomena and conformational cross-talk between a ligand and a receptor can in fact translate in unexplored opportunities for the discovery of new drug like molecules. We will illustrate and discuss dynamics-based pharmacophores, the discovery of cryptic binding sites, the characterization and exploitation of allosteric regulation mechanisms and the definition of potential protein-protein interaction sites as potential sources of new bases for the rational design of small molecules endowed with specific biological functions. Overall, the inclusion of protein flexibility in the drug discovery process is starting to attract attention not only in the academic but also in the industrial community. This is supported by experimental tests that prove the actual feasibility of considering the explicit dynamics of drug-protein interactions at all relevant levels of resolution and the use of multiple receptor conformations in drug discovery, as affordable complements (if not an alternative) to classical High Throughput Screening (HTS) efforts based on static structures.