Purpose of Review In the USA, fewer than 1% of people with Chagas disease (CD) are diagnosed and treated. Patients and physicians confront significant barriers to initiating testing and treatment, which are not systematically available in the US health care system. What are these barriers and how can they be overcome? We discuss the broader challenges and state-level dynamics of CD in several of the US states with the highest burdened populations. Recent Findings The principal challenges for expanding access to testing and treatment include confusion surrounding testing procedures, limitations in available drugs and diagnostic tools, gaps in surveillance and epidemiological knowledge, low patient awareness, and, particularly, low awareness among providers. States have key differences concerning health care access, transmission dynamics, and programmatic resources. Local initiatives in Texas and California are discussed. Summary Reducing the burden of CD will require improvement of diagnostic capacity and treatment guidelines, significant strengthening of provider awareness, greater understanding of transmission dynamics, and provision of accessible health care to the diverse population at risk.