The spectrum of pathologic processes affecting the midbrain features some differences to other brain areas. The midbrain is exposed to traumatic alterations due to its position between the tentorial edges, and some neurodegenerative and metabolic-toxic diseases may typically involve the midbrain. Isolated midbrain ischemia is rare, whereas the midbrain is typically part of the "top of the basilar" syndrome. Primary midbrain tumors are also infrequent and often show a benign clinical course. Apart from multiple sclerosis other inflammatory autoimmune processes and some infectious agents predominantly affect the brainstem including the midbrain. This review discusses the different pathologic processes of the midbrain, i.e., infarction, hemorrhage and trauma, inflammation, toxic and metabolic diseases, neurodegeneration, neoplastic diseases, as well as pathologies typically involving the perimesencephalic cisterns.