The lifecycle of most microbial pathogens can be divided into two states: existence outside and inside their hosts. The sudden temperature upshift experienced upon entry from environmental or vector reservoirs into a warm-blooded host is one of the most crucial signals informing the pathogens to adjust virulence gene expression and their host-stress survival program. This article reviews the plethora of sophisticated strategies that bacteria have evolved to sense temperature, and outlines the molecular signal transduction mechanisms used to modulate synthesis of crucial virulence determinants. The molecular details of thermal control through conformational changes of DNA, RNA and proteins are summarized, complex and diverse thermosensing principles are introduced and their potential as drug targets or synthetic tools are discussed.