Our bodies are under constant attack from pathogens. Despite this continual bombardment, under normal circumstances we remain healthy for most of our lives. This protection against infectious and harmful agents is provided by our immune system. The immune system can be broken into two elements: adaptive immunity and innate immunity. Adaptive immunity is a specific response targeted against particular pathogens through, for example, cytotoxic T cells and antibody production. The adaptive immune system has the potential to raise a defence against any invading pathogen. However, this is a relatively slow and energy expensive process. Innate immunity in contrast provides a non-specific response against any pathogen via a variety of components and processes. These include: barrier functions, complement, natural killer (NK) cells, antimicrobial peptides, mucosal secretions, pattern recognition receptors (PRRs) and the commensal micro-organisms. Innate immunity is responsible for clearing the majority of pathogen exposures that would result in infection before the adaptive system is even involved. This chapter will focus upon the role of one particular arm of the innate immune response to infectious diseases – Pattern Recognition Receptors. It will broadly address the mechanisms by which PRRs recognise the pathogens, the effects this has and the types if response it has. It will also bring in examples of evasion strategies used by pathogens to avoid detection and touch on the impact of polymorphisms in the receptors. Finally we will discuss the role of PRRs in a key defence against infectious diseases, vaccination.