Structure based drug design is now well established as a highly efficient approach in pharmaceutical research. The approach uses atomic level detail structures of target proteins, most generally determined through X-ray crystallography. For many years this approach has not been possible for the most common classes of drug targets, particularly membrane bound proteins such as GPCRs and transporters. Approximately 10 years ago, the first X-ray structures in these areas started to emerge and the determination of more structures has begun to accelerate in the recent past. These structures cover a rapidly increasing number of targets and categories including class A, B, C and F GPCRs, endogenous amine transporters. Included in these reports are proteins in various states, novel sites for ligand modulation and other characterizations. These reports have provided valuable information facilitating the design of new compounds with specific features such as intrinsic activity (from active to inactive), ligand bias, selectivity, allosterism and others. This growing body of information will be illustrated along with examples of successes and emerging new opportunities.