Palestine has a rich and prestigious heritage of herbal medicines. To investigate the impact of variable extraction techniques on the cytotoxic effects of medicinal plant extracts, 5 well-known medicinal plants from Palestine were extracted with 90% ethanol, 80% methanol, acetone, coconut water, apple vinegar, grape vinegar or 5% acetic acid. The resulting 35 extracts were screened for cytotoxic activities against three different cancer cell lines (B16F10, MCF-7 and HeLa) using a standard resazurin-based cytotoxicity assay and Nile Blue A as the positive control. Highly variable toxicities and tissue sensitivity were observed, depending upon the solvent used for extraction. The acetone extract of Salvia officinalis L. exhibited the most potent cytotoxicity (IC50 = 14 to 36 µg/ml), but very little sensitivity between the three cell lines. More moderate cytotoxicity with improved tissue sensitivity was observed with coconut water extract of S. officinalis L. (IC50 = 114 µg/ml) and methanol extract of Teucrium polium L. (IC50 = 104 µg/ml). In this study, acetone consistently gave lower extraction yields but higher cytotoxicity, whereas other solvent systems gave much higher extraction yields with lower cytotoxicity. These results demonstrate how the cytotoxicity of plant extracts can be inversely proportional to the yield, and that solvent selection plays an important role in both factors.