Antibiotic resistance has been a global threat for over twenty years. Combined therapy with antibiotics and natural antibacterial substances is one possible sustainable approach to the treatment of infections caused by bacteria capable of antibiotic resistance, such as the methicillin-resistant pathogen Staphylococcus aureus (MRSA). MRSA is a frequent cause of skin diseases in humans and livestock. Due to its content of a wide spectrum of bioactive substances, cannabis (Cannabis sativa L.) appears to be a promising plant with potential use in the fight against multiresistant bacteria. This review article discusses the skin microbiota, bacterial skin infections and its antibiotic treatment, which is challenged by bacterial resistance to different antimicrobial classes. Particular attention is also paid to the characteristics of C. sativa L., especially to the antibacterial effect of the substances in this plant and their synergistic potential in combination with antibiotics.