Nicotinic acetylcholine receptors (nAChRs) are master regulators of immune functions via the cholinergic anti-inflammatory pathway and are expressed in microglia, the brain’s resident immune cells. There is an extensive dialogue between the neurons and the glial cells around them from which microglia are tasked with monitoring, nurturing, and defending their microenvironment. Dysregulation of any of these processes can have devastating and long-lasting consequences involving microglia-mediated neuroinflammation associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, amongst others. Disease-associated microglia acquire a distinguishing phenotype that emphasizes scavenging and defence functions while nurturing and repairing functions become muted. Attempts to resolve this critical imbalance remain a key focus of research. Furthermore, cholinergic modulation of neuroinflammation represents a promising avenue for treatment.