Dysfunction of cholinergic signaling has emerged as a convergent mechanism across neurological and neuromuscular disorders, linking disturbances in synaptic, immune, and metabolic regulation. This review summarizes recent structural, functional, and imaging advances, demonstrating that nicotinic and muscarinic acetylcholine receptors play central roles in neural plasticity, neurotransmission, and neuroimmune homeostasis. Studies in structural biology and molecular pharmacology have clarified receptor architectures and conformational transitions, which enhance our understanding of subtype-specific ligand binding and signaling bias. This knowledge, in turn, supports the development of rational strategies for therapeutic modulation. In vivo molecular imaging using positron emission tomography and single-photon emission computed tomography has provided important insights into receptor distribution and binding changes in Alzheimer's disease, Parkinson's disease, schizophrenia, and myasthenia gravis. These findings suggest that impaired cholinergic tone contributes to synaptic instability, dopaminergic imbalance, and neuroinflammatory processes. Experimental and translational studies further indicate that selective agonists and positive allosteric modulators targeting cholinergic pathways can restore aspects of neurotransmission and neuronal function, supporting their potential for clinical translation. Beyond small-molecule pharmacology, the use of engineered exosome delivery systems and artificial intelligence-driven ligand discovery has opened new directions for improving receptor targeting and blood-brain barrier permeability. Although these emerging methods remain at an early stage, they offer valuable opportunities for optimizing receptor selectivity and drug delivery efficiency. Overall, the collective findings indicate that acetylcholine receptors act as integrative modulators of neuronal, glial, and immune communication. Continued integration of structural, imaging, and computational methodologies may help refine receptor-based therapeutic strategies. Such interdisciplinary efforts are expected to advance the development of more targeted and durable cholinergic interventions that promote neuronal resilience and functional recovery in neurological and neuromuscular diseases.