The treatment of acute and chronic pain is best delivered by utilizing multimodal strategies. From a pharmacological perspective, use of more than one pharmacological class of medication targeting different receptors along the pain pathway may allow for improved analgesia with reduced individual class-related side effects. Many nociceptive targets have been identified along with ligands that bind to them, but surprisingly few molecules make it successfully through the stages of analgesic development and FDA approval. The holy grail of analgesics would be a therapy that controls inflammatory, nociceptive, neuropathic and dysfunctional pain syndromes. This course will describe the limitations of currently approved analgesics, discuss the difficulties that agents in development have faced, and introduce promising molecules in various stages of clinical trials.