 Wesley Charles Salmon (1925–2001) was a central figure in twentieth century philosophy of science. Working in the tradition of Hume, Salmon developed a sophisticated version of empiricism combining a genuinely probabilistic approach with realism about theoretical entities. Salmon’s writings, characterized by a systematic and crystal-clear style, cover a wide range of topics including logic, the philosophy of space and time, the foundations of probability and scientific inference, rationality, realism, and scientific explanation, a major focus of his production for more than thirty years. Unlike the Hempelian “received view”, Salmon developed a concept of explanation according to which to explain means to exhibit the causal mechanisms responsible for the occurrence of phenomena. Convinced that our knowledge is uncertain and that causality ought to be defined in probabilistic terms, he pursued a probabilistic version of mechanicism, opening a new trend of research in the literature on explanation, known as “neo-mechanicism”. Salmon’s views on all the topics he addressed continue to nurture fresh reflection and ongoing debate.