Gas hydrates are known to occur in deepwater environments (low-temperature and high-pressure) at various locations across the globe. When they occur close to the sea bed, hydrates present challenges to drilling, completing, and producing in deepwater applications. Additionally, many operators now consider these as a potential resource when they occur deeper within the earth, and there is increased focus on feasibly producing methane from gas hydrates. Safety, environmental impact, and economic viability are the foremost challenges faced by the upstream oil and gas community to unleash the potential that these unconventional reserves hold for the future.Isolating the gas-hydrate-bearing zones by means of effective annular wellbore sealants is the prime factor that will contribute to the success of gas-hydrate campaigns. This paper addresses the current zonal isolation challenges likely to be encountered from the time drilling operation is completed until the plug and abandonment process is finished. With the considered lifecycle, a sealant system selection criteria based on commercially available technologies is proposed. While industry research on this front continues to progress, a holistic approach to designing a zonal isolation program to address the foreseeable challenges of unconsolidated formations, drilling-fluid removal in washouts, annular-sealant placement, battling lost circulation, prevention of hydrate destabilization, formation-fluid influx during the setting process, achieving good mechanical properties at low temperatures, and maintaining long-term sealing integrity throughout the life of the well is discussed and evaluated.The design approach involves (1) preliminary engineering sensitivity analysis to judge the effect of dominant parameters on sealant system design, (2) selection of commercially available, fit-for-purpose materials and laboratory testing, and (3) validation by means of confirmatory analyses. The approach presented is an incremental effort to help operators and industry researchers increase the productivity of gas-hydrate-bearing wells.