Pipeline infrastructure and its safety are critical for the recovering of U.S. economy and our standard of living. Diverse types of damage and failure can contribute to the overall pipeline integrity. A recent report has shown that, among many failures reported in the past few decades, it is likely that there are interactive threats which can lead to the final failure. These interactive threats have not been fully addressed in the existing knowledge. One critical example is the interaction of corrosion and weld, which will lead to earlier fracture of pipes. Thus, there is a clear gap which is solicited in the PHMSA announcement for additional research. Another critical gap is the systematic inclusion of uncertainties in the failure and risk assessment of these interactive threats. Some known sources of these uncertainties are: 1) material intrinsic randomness; 2) material spatial variability; 3) defect geometric and location variabilities; 4) manufacturing and installation variability; and 5) operational and environmental conditions. All these input uncertainties will contribute to the outcome of the failure assessment. Strategies for the reduction of impact of these uncertainties to the final pipeline assessment is critical to enhance the confidence in integrity assessment.