Calcium-activated chloride channels (CaCC) are expressed in almost every cell type and are implicated in a plethora of physiological functions, spanning from smooth muscle contraction to the control of cardiac and neuronal excitability. TMEM16A was recently found to encode the major component of CaCCs. The exact role of this protein in the tissues where CaCCs have been detected remains, however, largely unexplored: this issue is currently the subject of intense investigation by the scientific community. Potent and selective channel blockers would prove invaluable as pharmacological tools for TMEM16A research. Our work explored the ability of available chloride channel blockers to inhibit cloned human TMEM16A channels. Blockers studied were niflumic acid, 4,4′ diisothio-cyanatostilbene-2,2′-disulfonic acid (DIDS), tannic acid, penta-O-galloyl-β-D-glucose (PGG), epigallocatechin gallate (EGCG), flufenamic acid, mefenamic acid, meclofenamic acid, glibenclamide and T16Ainh-A01, a compound recently identified via high-throughput screening against TMEM16A. Human TMEM16A (splice variant, abcd) was permanently expressed in HEK-293 cells. Heterologous channel expression was verified using immunocytochemistry and whole cell patch-clamp recordings. The extent of inhibition that each compound produced on hTMEM16A mediated currents was measured in the presence of equimolar trans-membrane Cl- and ~103 nM intracellular free Ca2+. The selectivity of blockers was also explored by screening activity against 7 human cardiac ion channels (Cav1.2, Nav1.5, Kv7.1, Kv4.3, hERG, Cav3.2, Kv1.5) using IonWorks high-throughput patch clamp technique. None of the compounds tested presented complete selectivity for TMEM16A channels. Tannic acid was the least selective compound. It irreversibly inhibited TMEM16A with IC50=5±2µM (n=5), but also blocked 6 of the cardiac ion channels tested with IC50<100 µM. The most selective was DIDS, which reversibly inhibited TMEM16A with IC50=14±3µM (n=11). Although it inhibited Nav1.5 with similar potency, it did not block the other cardiac channels. T16Ainh-A01 blocked up to 60% of hTMEM16A current with an IC50 of 0.26 ± 0.09 µM (n=7). It also inhibited Nav1.5 and Kv7.1, but at concentrations 2 orders of magnitude higher (IC50=74 and 88 µM, respectively). This difference in potency suggests T16Ainh-A01 may be a selective blocker of TMEM16A if used at sub-μM concentrations. In general though, the currently available chloride channel blockers lack selectivity and are therefore not ideal pharmacological tools for TMEM16A research. This work highlights the need for the identification and development of more potent and selective hTMEM16A blockers.