In humans, exposure to endotoxins or pro-inflammatory cytokines induces a number of neuropsychological symptoms collectively referred to as 'flu-like syndrome'. The degree of overlap between flu-like syndrome and major depressive disorder is considerable and a close linkage between these has been predicted to arise due to hypersecretion of endogenous pro-inflammatory cytokines and activation of the hypothalamic pituitary adrenal axis. In animals, exposure to pro-inflammatory cytokines or endotoxins induces a 'sickness behavior' syndrome that is analogous to flu-like symptoms observed in human patients. The goal of the current paper is to review evidence implicating endotoxin- or cytokine-induced sickness behavior as an animal model of depression, with an emphasis on reduced consumption of highly palatable substances as a defining feature.