Populations of eastern black nightshade suspected of being resistant to acetolactate synthase (ALS) inhibitors have been reported since 1999 in different locations in Ontario, Canada. This event has threatened the use of ALS inhibitors for control of this species. The objectives of this study were to evaluate the spectrum of resistance to different ALS-inhibiting herbicides and to examine the effectiveness of alternative modes of action herbicides. Growth room experiments were conducted to determine the response to imazethapyr and atrazine in seven suspected ALS inhibitor– resistant populations. One resistant and one susceptible population were further characterized for their response to ALS inhibitors and chloroacetamides. Seven populations were able to survive imazethapyr at 100 g ai/ha, while there was no resistance to atrazine. Compared to a susceptible (S) population, resistant (R) population SOLPT 1 had 726-, 31-, 6-, and 4-fold resistance to postemergence (POST) applied imazethapyr, imazamox, primisulfuron, and flumetsulam, respectively. Preemergence (PRE) application of imazethapyr, flumetsulam, cloransulam, nicosulfuron, prosulfuron, and rimsulfuron did not provide control of the R population, whereas they totally controlled the S population. The chloroacetamide herbicides metolachlor, dimethenamid, and flufenacet all provided at least 90% control of both R and S populations when applied PRE at the recommended field rates. The ALS inhibitors will not provide adequate control of these resistant populations, but acceptable control could be achieved with chloroacetamides or with atrazine.