The Treat-to-Target (T2T) approach in rheumatoid arthritis (RA) emphasizes the systematic and regular adjustment of therapy based on predefined targets, typically remission or low disease activity. This review explores the evidence supporting the Treat-to-Target (T2T) strategy, its practical implementation, and its impact on comorbidities in rheumatoid arthritis (RA). Special attention is given to the role of biologics in managing RA, examining whether they effectively treat or reduce associated comorbidities. The review synthesizes findings from randomized controlled trials, meta-analyses, and real-world data to provide a comprehensive overview of T2T's theoretical framework and clinical practice.