The current paper reviews strategies employed by microorganisms from the deep biosphere, especially piezophiles (from the greek piezo = to press and philo = love), to cope with high hydrostatic pressure (HHP) prevailing in these biotopes. The aim of this review is not to constitute an exhaustive report of our current knowledge on the physiology of piezophiles, as recent reviews have covered part of this subject in detail (Abe, 2007; Lauro and Bartlett, 2008; Michiels et al., 2008; Simonato et al., 2006). Rather, we illustrate here, via a few chosen examples, where we stand in our understanding of the mechanisms employed by microorganisms from the depths of our planet to cope with HHP.