Neurodegenerative diseases exhibit a gradual onset and present a challenge due to the scarcity of specific biomarkers. While factors such as infection, trauma, and genetic mutation contribute to its development, the intricate interplay between the immune system and the central nervous system (CNS) of the body is widely implicated in causing damage of neurons in neurodegenerative disorders. The immune system assumes a distinctive role in both disease development/progression and cellular equilibrium of the body. It initiates cellular as well as humoral responses, which facilitates repairing of tissue, rejuvenation of cells, and the elimination of cellular waste. However, prolonged and aberrant activation of immune system can have detrimental effects on healthy neurons. The secretion of pro-inflammatory substances by key innate immune components such as microglia, compliment system, and inflammasomes can intensify cytotoxicity. Moreover, these inflammatory agents expedite the instigation of microglia, leading to a gradual decline in neuronal populations. The intricate interplay between the nervous and immune systems influences various aspects of CNS function, including immune surveillance, inflammation, neurogenesis, synaptic plasticity, and neurotransmission. This book chapter explores the significance of neuroimmune crosstalk in the context of neurological diseases, shedding light on the underlying mechanisms and potential therapeutic interventions.