Neurotransmitters and neuroreceptors are essential for neuronal communication and various physiological processes. Neurotransmitters, released by neurons, bind to specific neuroreceptors on target cells, altering electrical properties or initiating intracellular signaling. Neuroreceptors, classified into ionotropic and metabotropic types, regulate neuronal excitability and synaptic plasticity by controlling ion flow. Dysregulation of these systems can cause neurological and psychiatric disorders, making them key targets for therapies. This chapter examines the mechanisms of neuroreceptor endocytosis and its influence on cellular signaling. Endocytosis is a vital cellular mechanism that governs a range of neuronal functions, such as receptor signaling, neurotransmitter release, and membrane recycling. It plays a crucial role in neuronal growth and synaptic activities and involves both clathrin-dependent and clathrin-independent pathways. Rab GTPases are central to the regulation of endosomal trafficking. Neurotrophins, including nerve growth factor (NGF), interact with Trk receptors to support neuronal survival and axon growth, with signaling endosomes facilitating long-distance communication. In aging and neurodegenerative disorders like Alzheimer’s disease (AD), significant changes in neuroreceptor systems particularly in the cholinergic, dopaminergic, and serotonergic pathways, contribute to cognitive impairment. Advanced molecular imaging tools, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), have enhanced our understanding of these neuroreceptor changes, offering promise for earlier diagnosis and treatment. Further research is essential to better understand the complex interactions between neurotransmitter systems and their roles in aging and neurodegenerative conditions.