Candida pathogenesis involves exposure, adherence, colonization, and ultimately infection. Measures can be applied for each of these four aspects to prevent infections and improve outcomes in those infected. Invasive Candida infections in the NICU most commonly include bloodstream and urinary tract infections, meningitis, peritonitis, and congenital cutaneous candidiasis. NICU patients are at increased risk for invasive Candida infections due to their developing immune system and catheters and tubes that breech important protective barriers. Extremely preterm infants represent the highest-risk patients in the NICU, and incidence is inversely proportional to gestational age. Many studies demonstrate rates of invasive candidiasis >20% in infants less than 25 weeks gestation and decreasing to around 5% in 27 weeks gestation infants. Antifungal prophylaxis in high-risk patients is the most effective prevention measure and has been critically studied in randomized controlled trials. The highest-risk patients are infants <1000 g or <28 weeks gestation, in whom infection is associated with high mortality and neurodevelopmental impairment. For the entire NICU, a prevention bundle should include (1) targeted antifungal prophylaxis in high-risk patients (e.g., infants <1000 g or <28 weeks gestation), (2) infection control, (3) central line associated bloodstream infection (CLABSI) preventative practices, and (4) antibiotic, medication, and feeding stewardship. Infectious morbidity and mortality can be improved by (1) starting appropriate antifungal dosing, (2) adding antifungals to empiric therapy in high-risk patients or when there is a high suspicion for fungal infection, (3) prompt central venous catheter removal when candidemia is present, (4) prompt recognition of dermatologic findings of congenital or postnatal cutaneous candidiasis and then evaluation and systemic treatment for 14 days, and (5) end-organ dissemination screening. Future prevention may involve lactoferrin, probiotics, antifungal prophylaxis in patients with complex gastrointestinal diseases, and broader antenatal screening and treatment of vaginal Candida colonization and candidiasis.