In the past few decades, biodiesel has emerged as a promising renewable energy source. However, its production usually leads to the formation of large amounts of glycerol as a byproduct. This article reports the evaluation of catalytic glycerol etherification with ethanol over a series of catalysts in a continuous reactor. Amberlyst 15 presented the best performance in terms of glycerol conversion and yield of ethers. This result was attributed to its high pore size and acidity. Beta zeolite (Si/Al = 12.5) and niobic acid, both with lower acid strengths and pore sizes, were almost inactive in the conversion of glycerol into ethers. A central composite design was developed to optimize the performance of Amberlyst 15. An increase in catalyst amount enhanced both the glycerol conversion and the yield of ethers. However, high temperatures and low molar ratios favored side reactions. The optimized value for glycerol conversion was 91%, and that for the yield of ethers was 13%, under different reaction conditions.