Lithium–sulfur batteries (LSBs) are considered one of the most promising candidates for next-generation energy storage owing to their large energy capacity. Tremendous effort has been devoted to overcoming the inherent problems of LSBs to facilitate their commercialization, such as polysulfide shuttling and dendritic lithium growth. Pouch cells present additional challenges for LSBs as they require greater electrode active material utilization, a lower electrolyte–sulfur ratio, and more mechanically robust electrode architectures to ensure long-term cycling stability. In this review, the critical challenges facing practical Li–S pouch cells that dictate their energy density and long-term cyclability are summarized. Strategies and perspectives for every major pouch cell component—cathode/anode active materials and electrode construction, separator design, and electrolyte—are discussed with emphasis placed on approaches aimed at improving the reversible electrochemical conversion of sulfur and lithium anode protection for high-energy Li–S pouch cells.