A biofilm is a community of microorganisms that adhere to each other and to surfaces and secrete extracellular polymeric substances (EPS) encasing themselves in a matrix. Biofilms are a major healthcare concern, as they can form on medical devices leading to infection. Additionally, there is growing evidence to show their ability to form in chronic wounds, which leads to delayed wound healing and inflammation. Due to a number of reasons, such as formation of the EPS resulting in sub-inhibitory concentrations of antimicrobials reaching the bacterial cells, slow growth rate of bacterial cells rendering some antibiotics ineffective, and the presence of persister cells, biofilms show increased tolerance to many antimicrobials and antibiotics. Additionally, studies have started to emerge showing a link between resistance to antimicrobials and antibiotics. Cross-resistance can be attributed to a number of factors, for example, increased expression of multidrug efflux pumps that efflux a wide range of substrates and horizontal gene transfer of genetic material encoding multiple resistance genes between different species within the polymicrobial biofilm. Antimicrobial resistance is an increasing threat caused by multiple factors including cross-resistance, and it is a global health concern. This review focuses on current research on antimicrobial and antibiotic resistance and cross-resistance found between antimicrobials and antibiotics commonly used in woundcare to evaluate the significance of this acquired antibiotic resistance. Furthermore, the review discusses the significance of antimicrobial tolerance and the role biofilms play in enhancing antibiotic resistance.