Prognosis and outcome are two terms routinely used in medicine and dentistry to predict and assess the treatment of disease. Prognosis is a practitioner’s assessment about how a patient will recover from an illness or injury. It is a forecast of the probable course of recovery for any particular disease considering the assessment of the case. Outcome is the end result of the treatment and a consequence of treatment decisions made by the practitioner. In endodontics, there are prognostic factors which are universal to all cases as well as variables unique to a specifc case, all of which can affect endodontic treatment outcomes. Prognostic factors can be grouped into preoperative, intraoperative, and postoperative. They influence endodontic treatment outcomes indirectly through control and elimination of infection. Importantly, an understanding of prognostic factors helps practitioners as well as patients decide the appropriate treatment procedures and is especially important for higher-risk conditions such as teeth with a periapical lesion, calcifed canals, resorption, and others. This applies to immature or mature teeth for consideration for nonsurgical or surgical management. Although many prognostic factors are not under the control of the practitioners, they can nevertheless be managed by a practitioner’s thorough evaluation of the presenting condition, risk assessment inherent in each individual case, and application of biologically based therapies alongside with technical competency.