The health of dairy animals, particularly the milk-producing mammary glands, is essential to the dairy industry because of the crucial hygienic and economic aspects of ensuring production of high quality milk. Due to its high prevalence, mastitis is considered the most important threat to dairy industry, due to its impacts on animal health and milk production and thus on economic benefits. The MG is protected by several defence mechanisms that prevent microbial penetration and surveillance. However, several factors can attenuate the host immune response (IR), and the possession of various virulence and resistance factors by different mastitis-causing microorganisms greatly limits immune defences and promotes establishment of intramammary infections (IMIs). A comprehensive understanding of MG immunity in both healthy and inflammatory conditions will be an important key to understand the nature of IMIs caused by specific pathogens and greatly contributes to the development of effective control methods and appropriate detection techniques. Consequently, this review aims to provide a detailed overview of antimicrobial defences in the MG under healthy and inflammatory conditions. In this sense, we will focus on pathogen-dependent variations in IRs mounted by the host during IMI and discuss the potential ramifications of these variations.