AbstractHistorically, typhoid control has been achieved with water and sanitation interventions. Today, in an era of rising antimicrobial resistance (AMR), two World Health Organization-prequalified vaccines are available to accelerate control in the shorter term. Meanwhile, water and sanitation interventions could be implemented in the longer term to sustainably prevent typhoid in low- and middle-income countries. This article first approaches typhoid control from a historical perspective, subsequently presents how vaccination could complement water and sanitation activities, and finally discusses the challenges and opportunities for impactful control of typhoid infection. It also addresses data blind spots and knowledge gaps to focus on for typhoid control and to ultimately progress towards elimination. This article presents a synthesis of discussions held in December 2021 during a roundtable session at the “12th International Conference on Typhoid and Other Invasive Salmonelloses”.