In addition to circadian rhythms, circadian genes play pivotal roles in myriad signaling pathways. Consequently, their dysregulation contributes to the onset and progression of various diseases.Identifying SNPs in clock genes offers an exciting avenue to predict the predisposition of an individual to different pathologies/variations in phenotype.Experimental models and human trials have confirmed that SNPs in core circadian genes are associated with pathologies.Given the inherent complexity of diseases, that are often polygenic traits influenced by gene–environment interactions, robust statistical approaches utilizing large and diverse sample sizes is crucial when identifying disease-linked SNPs. Furthermore, recognizing the key role of population stratification in minimizing confounding effects ensures the reliability of associations between SNPs and diseases. Circadian rhythms, ~24 h cycles of physiological and behavioral processes, can be synchronized by external signals (e.g., light) and persist even in their absence. Consequently, dysregulation of circadian rhythms adversely affects the well-being of the organism. This timekeeping system is generated and sustained by a genetically encoded endogenous mechanism composed of interlocking transcriptional/translational feedback loops that generate rhythmic expression of core clock genes. Genome-wide association studies (GWAS) and forward genetic studies show that SNPs in clock genes influence gene regulation and correlate with the risk of developing various conditions. We discuss genetic variations in core clock genes that are associated with various phenotypes, their implications for human health, and stress the need for thorough studies in this domain of circadian regulation. Circadian rhythms, ~24 h cycles of physiological and behavioral processes, can be synchronized by external signals (e.g., light) and persist even in their absence. Consequently, dysregulation of circadian rhythms adversely affects the well-being of the organism. This timekeeping system is generated and sustained by a genetically encoded endogenous mechanism composed of interlocking transcriptional/translational feedback loops that generate rhythmic expression of core clock genes. Genome-wide association studies (GWAS) and forward genetic studies show that SNPs in clock genes influence gene regulation and correlate with the risk of developing various conditions. We discuss genetic variations in core clock genes that are associated with various phenotypes, their implications for human health, and stress the need for thorough studies in this domain of circadian regulation.