: Owing to the evolution of resistant cells using standard antimicrobial methods, it is necessary for us to find alternative strategies to block the attack without exerting pressures on their duplicated structures and in some cases degradation of their Quorum Sensing signals is suggested to be more efficient. In this chapter, we give a brief introduction of quorum sensing basics. Then, we describe the computational approaches that are used to find molecules to inhibit the chemical signals. After that, we present the case studies using these computational methods. In one of the cases performed in E. coli with the autoinducer molecule indole, we elaborate how to evaluate and find molecules with the ability to degrade the indole. We present another case where biological molecules with potential ability to degrade the autoinducer 3-OH-PAME Quorum Sensing system in R. solanacearum were evaluated as potential quenchers.