Hardware Performance Counters (HPCs) have been available in processors for more than a decade. These counters can be used to monitor and measure events that occur at the CPU level. Modern processors provide hundreds of hardware events that can be monitored, and with each new processor architecture more are added. Yet, there has been little in the way of systematic studies on how performance counters can best be utilized to accurately monitor events in real-world settings. Especially when it comes to the use of HPCs for security applications, measurement imprecisions or incorrect assumptions regarding the measured values can undermine the offered protection.To shed light on this issue, we embarked on a year-long effort to (i) study the best practices for obtaining accurate measurement of events using performance counters, (ii) understand the challenges and pitfalls of using HPCs in various settings, and (iii) explore ways to obtain consistent and accurate measurements across different settings and architectures. Additionally, we then empirically evaluated the way HPCs have been used throughout a wide variety of papers. Not wanting to stop there, we explored whether these widely used techniques are in fact obtaining performance counter data correctly. As part of that assessment, we (iv) extended the seminal work of Weaver and McKee from almost 10 years ago on non-determinism in HPCs, and applied our findings to 56 papers across various application domains.In that follow-up study, we found the acceptance of HPCs in security applications is in stark contrast to other application areas — especially in the last five years. Given that, we studied an additional representative set of 41 works from the security literature that rely on HPCs, to better elucidate how the intricacies we discovered can impact the soundness and correctness of their approaches and conclusions. Toward that goal, we (i) empirically evaluated how failure to accommodate for various subtleties in the use of HPCs can undermine the effectiveness of security applications, specifically in the case of exploit prevention and malware detection. Lastly, we showed how (ii) an adversary can manipulate HPCs to bypass certain security defenses.