In discussing open question in the field of massive stars, I consider their evolution from birth to death. After touching upon massive star formation, which may be bi-modal and not lead to a zero-age main sequence at the highest masses, I consider the consequences of massive stars being close to their Eddington limit. Then, when discussing the effects of a binary companion, I highlight the importance of massive Algols and contact binaries for understanding the consequences of mass transfer, and the role of binaries in forming Wolf-Rayet stars. Finally, a discussion on pair instability supernovae and of superluminous supernovae is provided.