It is widely accepted that sigma (σ) receptors represent a new and different avenue in the possible pharmacological treatment of cancer and several brain-related disorders. Of the two different σ receptor types the σ1 receptors are assumed to be of major impact for brain diseases. Molecular imaging of brain σ1 receptors with positron emission tomography (PET) or single photon emission computed tomography (SPECT) may provide a significant contribution to the understanding of the cross-talk between σ1 receptors and inter- and intracellular signalling systems. New insights into these functional interrelationships will allow a better diagnosis of brain and cancerous diseases and direct a rational development of new therapeutic concepts.