The Hamilton & Zuk hypothesis (1982) underpins our understanding of the relationship between secondary sexual characters, parasites, and immunological function. However, despite the wealth of empirical studies that attempt to address issues raised by the Hamilton & Zuk hypothesis, there have been no overt attempts to identify the “good genes” that females select or how those good genes influence the host’s immune system. Behavioural ecologists have generally viewed this aspect of immunity as a black box. In this review we propose candidate good genes in vertebrates, discuss their role in immune function and parasite resistance, and discuss several aspects of the assumptions that pervade studies of parasite mediated sexual selection in vertebrates. We also examine invertebrates (specifically insects) where our current knowledge of these systems suggests the patterns apparent in vertebrates are not underpinned by the same genetic mechanisms.