Actinomyces species are opportunistic pathogens, difficult to isolate, and often accompanied by other pathogens. We report the case of an immunocompetent woman who presented with respiratory distress and was discovered to have a right-sided empyema requiring chest tube drainage. Streptococcus species and Actinomyces odontolyticus were isolated in pleural fluid cultures. Initial empiric broad-spectrum antibiotic therapy and chest tube placement failed to show clinical improvement. Upon isolation of Actinomyces, the treatment was streamlined to ampicillin/sulbactam while pleural drainage continued, producing significant clinical status improvement in the patient. Given the known co-pathogenicity of Actinomyces species and the difficulty in isolating Actinomyces, it is essential to consider antibiotic coverage for Actinomyces species in those with Streptococcus species empyema.