Bacterial infections, particularly those due to gram-positive bacteria, continue to predominate in patients with cancer. Coagulase-negative and coagulase-positive staphylococci and enterococci remain as common pathogenic microorganisms. Clostridium difficile has emerged as a significant pathogen. Major clinical syndromes include vascular catheter-related infection, febrile neutropenia, diarrhea and colitis. Rising antimicrobial resistance among gram-positive bacteria is of serious concern. The clinical utility of penicillin against streptococci and vancomycin against coagulase-negative and coagulase-positive staphylococci and enterococci may be rapidly diminishing. Liberal empiric use of vancomycin during neutropenic fever needs careful reconsideration. Newer promising anti-gram-positive bacterial drugs with activity against methicillin-resistant staphylococci include daptomycin, linezolid, tigecycline and telavancin. However, toxicity concerns, limited data in immunocompromised populations and high cost prevent the widespread use of these drugs among patients with cancer.