Cobalt-based Fischer–Tropsch synthesis (FTS) catalysts are an integral part of the gas-to-liquid (GTL) process. Due to the cost of both cobalt and noble metals, which are often used as promoters, an extended catalyst life is required to make the process economically feasible. Fundamental understanding of the deactivation mechanisms at play during FTS is key to extending catalyst lifetime. Most of the research on cobalt catalyst deactivation in the last 15 years has focused on oxidation as a deactivation mechanism. From our work it can be concluded that oxidation is not a deactivation mechanism during FTS for supported Co catalysts with crystallite size in excess of 2 nm. On the contrary the FT environment was found to be strongly reducing. Following a comprehensive study into the deactivation of a cobalt catalyst under realistic FTS conditions the following intrinsic deactivation mechanisms were identified: (1) sintering of Co active phase, (2) carbon deposition and (3) surface reconstruction. Having identified these mechanisms a three-step regeneration process, i.e.: (1) dewaxing (2) oxidation and (3) reduction, was tailored to reverse the sintering, carbon deposition and surface reconstruction that takes place during FTS.