Solvents have been used in endodontic retreatment for a long time and the dissolving effect is well proven. Latterly chloroform has come in a bad light due to its possible carcinogenicity. Despite the negative health effect it is still used in dental environment. Other more biocompatible solvents have now reached the market and tests should be performed to evaluate the softening efficacy. The purpose of this in-vitro study was to evaluate the softening efficacy of four different solvents used in endodontics; chloroform, eucalyptol, tetrachloroethylene, orange-oil and a control group. 100 simulated canals filled with gutta-percha, epoxy amine resin based sealer, zinc oxide eugenol based sealer and non eugenolcalcium hydroxide based sealer were tested with hardness measurement before and after two minutes exposure time of medicament. Non-eugenol calcium hydroxide failed to set and was excluded from the test. A Shore A durometer was used to evaluate the hardness of the materials and all data was first analyzed with Kruskal-Wallis test and then Mann-Whitney test to compare with control group. With a digital camera connected to a microscope we also took pictures to compare the impressions with the different medicaments. The result showed that chloroform and tetrachloroethylene is significant better to soften gutta-percha than control group (p < 0.05) but only chloroform significant better than control group to soften epoxy amine resin based sealer and zinc oxide eugenol based sealer (p < 0.05). Even if the result was significant, we cannot draw any conclusions due to small sample size.