Benzathine penicillin G is an important antibiotic for the treatment and prevention of group A streptococcal infections associated with rheumatic fever and rheumatic heart disease. However, as rheumatic heart disease has receded as a public health priority in most high-income settings, attention to the supply, manufacture, and accessibility of benzathine penicillin G has declined. Concerns about the quality, efficacy, and innovation of the drug have emerged following plasma analysis and anecdotal reports from low-resource settings. This review collates core issues in supply and delivery of benzathine penicillin G as a foundation for concerted efforts to improve global quality and access. Opportunities for intervention and improvement are explored.