Bicuspid aortic valve (BAV) is a syndromic condition characterized by two cusps instead of the three in the aortic valve, associated with aortopathy and cause of valve incompetence and aortic dissection. This common congenital heart defect affecting 1–2% of the population shows familial clustering with 4–11% prevalence in first-degree relatives, suggesting autosomal dominant inheritance with reduced penetrance and variable expressivity. This chapter extensively discusses key genes and pathways implicated in BAV development. The NOTCH signaling pathway, particularly the NOTCH1 gene, plays a crucial role in valve formation and has been linked to both sporadic and syndromic BAV cases. The GATA transcription factor family, including GATA4, GATA5, and GATA6, is vital for heart valve differentiation and has been associated with BAV through various studies. The TGF-β signaling pathway, involving genes like SMAD6 and TBX20, contributes to valve development and has been implicated in both syndromic and non-syndromic BAV. The Slit-Robo signaling pathway, with genes such as ROBO1 and ROBO4, has emerged as a significant player in BAV etiology. Recent genome-wide association studies have identified additional risk loci, including genes involved in cilia function (EXOC4, EXOC6, EXOC8) and others like PALMD, TEX41, MYH6, and MUC4, further expanding our understanding of the complex genetic architecture of BAV. Copy number variations account for up to 10% of cases, particularly in patients with early onset or severe complications. Despite significant advances, the majority of familial BAV cases remain genetically unresolved, indicating a complex interplay of multiple genes and environmental factors, and official guidelines for clinically actionable genes are still lacking. Nevertheless, clinical and genetic evaluations in families are recommended to identify members at risk of complications due to the conditions.