INTRODUCTION: This review considers special populations as those patients for whom Gram-positive infections are particularly challenging to treat. We examine the potential benefits of dalbavancin in these patients. AREAS COVERED: We focus on patients with renal impairment, hepatic failure or obesity, and, also, pediatric patients, elderly patients and socially vulnerable individuals. Five independent experts conducted exhaustive literature searches on PubMed. Papers were selected for inclusion according to their relevance to the topic. For each special population, we outline the most significant characteristics for infection management, describing the challenges of the most frequent Gram-positive infections, and reviewing the potential role of dalbavancin. EXPERT OPINION: Dalbavancin may be a valid alternative to overcome the difficulties of infection management in these populations. We hope our insights will prove useful for patient-centered care. A long half-life, evidence-based efficacy and good safety profile make dalbavancin an adequate option, particularly for patients for whom oral treatment or continued IV access may be challenging, or those for whom hospital stay is more impactful.