Sigma receptors have been implicated in a myriad of cellular functions, biological processes and diseases. While the precise biological functions of sigma receptors have not been elucidated, recent work has shed some light on to these enigmatic systems. Sigma receptors have recently been a target of drug development related to psychiatric and neurological disorders. Sigma ligands have also been shown to modulate endothelial cell proliferation and can control angiogenesis which makes them a promising target for oncology applications. Other areas currently being investigated include treatment of gastrointestinal, cardiovascular, endocrine and immune system disorders. Of interest is that the human sigma-1 receptor gene contains a steroid binding component, and several gonadal steroids, including progesterone, testosterone and dehydroepiandrosterone (DHEA), interact with sigma-1 receptors. Of the steroids examined thus far, progesterone binds with the highest affinity to human sigma-1 receptors, with a reported affinity (Ki) as high as 30 nM while the other steroids exhibit lower affinity. For this and other reasons, sigma-1 receptors have been proposed as a link between the central nervous system and the endocrine and reproductive systems. Taken together, the above information highlights an important yet largely unexplored but promising area of research to examine the biological function and therapeutic potential of sigma receptors. This review provides an overview of the current knowledge of these sites with a focus on specific areas where in vivo sigma receptor imaging is currently being investigated.