Toll-like receptors (TLRs) are important innate immune proteins, and the activation of the TLRs results in the activation of intracellular signaling pathways, leading to the expression of proinflammatory cytokines that are essential to the identification and clearance of invading pathogens. TLR signaling occurs through adaptor proteins, most commonly myeloid differentiation primary response gene 88 (MyD88). It is now known that immune surveillance and inflammatory responses occur in neurodegenerative diseases and TLR/MYD88 signaling plays a critical role in these diseases. The included studies suggest a contribution for this signaling to the pathophysiology of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple system atrophy, and related disorders. In this review, a discussion of the recent findings in this field is presented.