Although neurotrophins of the nerve growth factor (NGF) family are best known for their neurite outgrowth-inducing and survival-promoting effects on neuronal cells, these are actually pleiotropic growth factors acting physiologically on many different cell types of our body. As for many other growth factors, dysregulation of neurotrophin signal transduction is found in a number of tumors where they can accompany or contribute to malignant transformation. Interestingly, tropomyosin-related kinase (Trk) receptor activation can either support or suppress tumor growth, depending on the tumor type. These same divergent responses have been observed with neurotrophins binding to the p75NTR neurotrophin receptor on tumor cells. This article summarizes the current knowledge on the role of neurotrophins and their receptors in malignancies, with special focus on tumors of neuropathological interest.