Resistance to pathogens is one of the most ancient traits; mechanisms for discriminating self from non-self have evolved to accomplish this task. Animal and plant immune systems use a set of similar receptors to recognize pathogens. These receptors are located either at the cell surface or inside the cell. Kinases modulate further signalling and are either associated to the receptors or are part of the receptors themselves. In this review, we compare gene families and the nucleotide binding (NB) and the Toll-interleukin-1 receptor (TIR) domains of various kingdoms that are important for the immune systems. Possibilities to deconstruct and reconstruct evolutionary events contributing to the immune systems are explored together with functional aspects.