Direct urea fuel cell (DUFC) is an attractive and inexpensive method for the simultaneous wastewater treatment (urine and urea-contaminated water) and electricity generation. Many efforts have been made to increase the catalytic activity of Ni-based DUFC anodic catalyst toward urea oxidation, which is considered to be the best non-precious catalyst in alkaline media so far. Alloying Ni with other metals and/or non-metals, and increasing its surface area demonstrated a power of up to 26.9 mW cm(-2) at room temperature, which is comparable to that obtained in direct alcoholic fuel cells using high loading of precious catalyst. However, this is still viewed as low performance. This review presents a comprehensive picture of the mechanism of urea oxidation on Ni-based catalysts, the poisoning effect of catalysts and its possible remedies, as well as the different approaches in preparing highly active catalysts. We also analyze the performance and associated issues of DUFC using newly applied strategies to increase its open-circuit voltage and power output via alternative oxidants and re-designed chemical conditions in the cell.