Background: Rapidly growing mycobacterial species (RGM) are increasingly being recognized as the cause of various superficial and deep infections in humans. Two of the species most frequently isolated from clinical specimens are Mycobacterium abscessus and Mycobacterium fortuitum. Both species are associated with antibiotic resistances that may complicate therapy. This paper describes the pattern of resistance to five antibiotics commonly prescribed for RGM infections, in M. abscessus and M. fortuitum isolated from Malaysian patients. Methods: The bacterial strains studied were examined with Etest strips to determine their minimum inhibitory concentrations (MICs) toward amikacin, ciprofloxacin, clarithromycin, imipenem, and linezolid. Results: Among 51 M. abscessus isolates examined by the Etest, the overall MICs of ciprofloxacin, imipenem, amikacin, clarithromycin, and linezolid showed resistance rates of 33.3%, 31.4%, 2.0%, 5.9%, and 21.6%, to the five antibiotics, respectively. M. abscessus subspecies abscessus was more resistant than M. abscessus subsp. massilience to ciprofloxacin, imipenem, and linezolid but was more susceptible to clarithromycin and amikacin. M. fortuitum isolates were significantly less resistant than M. abscessus to ciprofloxacin (3.6%) and imipenem (7.1%) but more resistant to clarithromycin (42.9%) and linezolid (39.3%). Conclusion: A suitable combination therapy for Malaysian patients would be amikacin plus clarithromycin and ciprofloxacin, to cover infections by all three M. abscessus subspecies and M. fortuitum.