Saliva plays an important role in the maintenance of oral health and regulation of the oral microbiota. Saliva lubricates the oral hard and soft tissues, dilutes food detritus and bacteria and enhances the clearance of microorganisms and dietary carbohydrates from the oral cavity. Saliva also provides antimicrobial activity via numerous proteins and peptides including lactoferrin, lactoperoxidase, lysozyme, statherin and histatins. This chapter focuses on the oral microbiota in patients suffering from salivary gland hypofunction due to Sjögren’s syndrome, radiotherapy of tumours in the head and neck region, cancer chemotherapy and intake of medications. Despite the different causes of salivary gland hypofunction, these patient groups show some similarities regarding the composition of the oral microbiota with increased colonisation of oral pathogens associated with dental caries (Streptococcus mutans and Lactobacillus species) and oral mucosal infections, especially Candida albicans.