Early-onset neonatal sepsis (EONS) is one of the major causes of mortality in neonates, especially in very low irth weight infants. EONS has no specific manifestations, and progresses rapidly and unexpectedly. EONS is often missed diagnosed r even misdiagnosed due to the absence of ideal diagnostic methods in current clinical practice, and this dilemma leads to he high mortality of EONS. Therefore the accurate diagnosis in the early stage of EONS is very important. This review describes the progress in diagnostic methods of EONS including culture, blood cell counts, molecular biological technique, procalcitonin and C-reactive protein measurements, cytokine profiling and some other novel means. It may provide useful information for early diagnosis of EONS.