The vast majority of rare diseases are of genetic origin, and a comprehensive understanding of inheritance models is essential for elucidating their molecular pathogenesis, improving diagnostic accuracy, and developing targeted therapeutic strategies. Today, inheritance models are no longer regarded solely as mechanisms of transmission across generations but rather as integrated biological frameworks encompassing gene function, protein biology, cellular pathways, and genotype–phenotype relationships. In this chapter, autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, Y-linked, mitochondrial, and complex/multifactorial inheritance models are examined from a contemporary molecular genetics perspective. Each inheritance model is discussed in relation to representative diseases, causative genes, their encoded proteins, molecular and cellular pathogenic mechanisms, phenotypic variability, genotype–phenotype relationships, and clinical management approaches. In addition, the impact of different inheritance models on disease severity, clinical heterogeneity, prognosis, and therapeutic response is evaluated. Recent advances in genomic technologies, next-generation sequencing, and functional genomics have substantially improved our understanding of the molecular basis of inheritance. These developments have contributed to more accurate disease classification, increased molecular diagnostic yield, and the broader implementation of precision medicine approaches. Collectively, inheritance-based classifications provide a fundamental framework for understanding the biological diversity of rare diseases and represent a cornerstone of modern genomic medicine.