Search for the ideal radiopharmaceutical to measure effective renal plasma flow (ERPF) has been underway since the early 1960s. Although ortho-iodohippuran (OIH) has biological properties suited for measurement of ERPF, the imaging characteristics are less than desirable. With the advent of the molybdenum-99/technetium-99m generators, efforts have focused on the development of a technetium-99m agent to measure ERPF. Over the last 10 to 15 years several promising technetium-99m renal imaging agents have been developed. Early examples of technetium-99m renal agents such as 99mTc-CO2DADS and 99mTc-PAHIDA, although not ideal replacements for OIH, demonstrated that a technetium-99m complex could be actively transported by the renal tubules and provided the impetus for development of new technetium-99m renal agents. The next breakthrough in technetium-99m renal agents was the development of the triamide mercaptide class of chelating agents by Fritzberg et al. To date the most promising compound in this class is mercaptoacetyltriglycine (MAG3). 99mTc-MAG3 is currently the agent of choice, but it is by no means the perfect replacement for OIH. Problems with high plasma protein binding and clearances that are only 50% to 60% of the OIH clearance make measurement of ERPF difficult. The serendipitous discovery that metabolites of the brain agent 99mTc-ethylenedicysteine diethylester (99mTc-L,L-ECD) are rapidly excreted in the urine has led to the evaluation of 99mTc-L,L-ethylenedicysteine (99mTc-L,L-ECD) as a potential renal imaging agent. Studies that have evaluated 99mTc-L,L-EC in animals, normal human volunteers, and patients with various renal disorders reveal that the renal clearance of 99mTc-L,L-EC is higher than 99mTc-MAG3 and more closely approaches that of OIH. Other approaches that are being examined in the development of the ideal renal imaging agent include substitution of various amino acids for glycine residue in MAG3 and technetium-99m labeled organic cations.