This chapter provides a comprehensive analysis of well integrity in the context of Carbon Capture and Storage (CCS), where long-term containment of CO₂ in deep geological formations is critical for climate mitigation. CCS wells, often repurposed from oil and gas operations or newly drilled in saline aquifers and depleted reservoirs, face unique integrity risks stemming from the chemical reactivity of supercritical CO₂, elevated pressures, thermal gradients, and potential reactivation of pre-existing faults or fractures. Ensuring robust zonal isolation and preventing CO₂ migration are paramount for environmental and regulatory compliance. The chapter begins by examining the geochemical environment created by CO₂ injection, highlighting degradation mechanisms affecting Portland cement (e.g., carbonation, leaching, and strength reduction) and steel casings (e.g., corrosion under acidic conditions). It introduces experimental and field-based evidence on CO₂-induced damage to wellbore materials and evaluates long-term stability using reactive transport models. Self-healing cements, pozzolanic additives, and CO₂-resistant coatings are discussed as emerging technologies for improving barrier performance. Mechanically, CO₂ injection alters the stress regime in the wellbore and surrounding formation, potentially leading to thermal fracturing, cement debonding, and micro-annulus formation. Coupled thermo-hydro-mechanical (THM) simulations are presented to assess risk scenarios for leakage pathways, particularly in legacy wells with incomplete or deteriorated primary barriers. Field experiences from projects such as Sleipner, Quest, and Illinois Basin–Decatur are used to illustrate lessons in well design, monitoring, and remediation. The chapter emphasizes the importance of risk-based integrity assessments, including pre-injection wellbore diagnostics, cement bond evaluation, annular pressure testing, and long-term pressure/temperature monitoring. It introduces the concept of the “smart injection field,” incorporating fiber-optic sensing, distributed acoustic measurements, and digital twin technologies to enable real-time integrity management. Plugging and abandonment of CCS wells pose additional integrity challenges, requiring the use of permanent barriers that resist CO₂ attack for hundreds to thousands of years. Regulatory frameworks (e.g., EPA Class VI, ISO 27914) are reviewed, along with evolving best practices for long-term liability and post-injection site care. By integrating geomechanical, geochemical, and operational insights, this chapter offers a holistic framework for designing, operating, and decommissioning CCS wells with verifiable integrity, positioning CCS as a viable pillar of global decarbonization strategies.