Renal fibrosis, particularly tubulointerstitial fibrosis, is a common outcome of progressive chronic kidney diseases and a significant predictor of poor prognosis. The process of renal fibrogenesis involves four overlapping phases: priming, activation, execution, and progression. Nonresolving inflammation after sustained injury sets the stage for fibrogenesis, activating matrix-producing cells from various sources through diverse mechanisms. These cells assemble a multicomponent, integrin-associated protein complex that integrates fibrogenic signals and orchestrates matrix production. Key cellular and molecular events, such as tubular atrophy, microvascular rarefaction, and tissue hypoxia, promote scar formation and contribute to the progression to end-stage kidney failure. This review outlines the current understanding of the cellular and molecular mechanisms of renal fibrosis, highlighting the complex interplay between inflammation, fibroblast activation, and the production of extracellular matrix components. The review also discusses the role of specific signaling pathways, such as NFκB and integrin-linked kinase (ILK), in the regulation of matrix production and the formation of the 'matrisome,' a molecular platform that integrates fibrogenic signals. Finally, the review addresses the challenges and future directions in the field, emphasizing the need for further research to develop effective therapeutic strategies for renal fibrosis.Renal fibrosis, particularly tubulointerstitial fibrosis, is a common outcome of progressive chronic kidney diseases and a significant predictor of poor prognosis. The process of renal fibrogenesis involves four overlapping phases: priming, activation, execution, and progression. Nonresolving inflammation after sustained injury sets the stage for fibrogenesis, activating matrix-producing cells from various sources through diverse mechanisms. These cells assemble a multicomponent, integrin-associated protein complex that integrates fibrogenic signals and orchestrates matrix production. Key cellular and molecular events, such as tubular atrophy, microvascular rarefaction, and tissue hypoxia, promote scar formation and contribute to the progression to end-stage kidney failure. This review outlines the current understanding of the cellular and molecular mechanisms of renal fibrosis, highlighting the complex interplay between inflammation, fibroblast activation, and the production of extracellular matrix components. The review also discusses the role of specific signaling pathways, such as NFκB and integrin-linked kinase (ILK), in the regulation of matrix production and the formation of the 'matrisome,' a molecular platform that integrates fibrogenic signals. Finally, the review addresses the challenges and future directions in the field, emphasizing the need for further research to develop effective therapeutic strategies for renal fibrosis.