The management of drug-use associated endocarditis (DUA-IE) has historically been piece-meal with variable involvement of multiple specialties - cardiology, addictions medicine, infectious disease, surgery and others. The literature was reviewed and combined with the writing group's insights from years of clinical experience to come up with recommendations for care. In this review, the potential benefits of providing holistic, person-centered, multidisciplinary care to these patients are discussed. The diagnosis of a patient with DUA-IE provides an opportunity to not only treat their presenting condition, but to screen for co-infections, address socioeconomic barriers, and connect with longitudinal care. Moreover, there is an ongoing paradigm shift towards the use of partial-oral antibiotic regimens which may reduce barriers to access and adherence for this population. Variability in whether surgery is offered for persons who inject drugs exists, especially in relation to first expecting abstinence, however this is a non-evidence-based criterion to determine operative candidacy. Decisions around timing and type of surgical intervention should be made systematically with the support of a multi-disciplinary team to avoid bias and achieve the best possible clinical outcome. Regarding management of substance use, data exists to support harm reduction strategies including provision of sterile substance use equipment, opioid agonist therapy, overdose prevention, take-home naloxone programs, drug checking services, and supportive housing programs. The mobilization of a multi-disciplinary endocarditis team is fundamental for providing the best possible care, which should be individualized.