This narrative review integrates human, animal, and in vitro evidence to examine the dual-axis organization of the joint RAS, comprising a pathogenic angiotensin-converting enzyme (ACE)/Angiotensin II (Ang II)/ Angiotensin II type 1 receptor (AT1R) axis and a counter-regulatory ACE2/Angiotensin-(1-7) (Ang-(1-7))/Mas receptor-Mas related G protein-coupled receptor D (Mas-MrgD) axis, and to explore how imbalance between these pathways may differentially influence inflammatory and degenerative joint diseases. This evidence concerns the gene AGT and osteoarthritis.