Purpose: This study aims to examine the new challenges for human resource management amidst the COVID-19 pandemic with implications for HR professionals in dealing with their employees. Approach/Methodology: The study is a general review that attempts to explore the impact of COVID-19 on human resource management. Between December 2019 and July 2021, the researchers did a manual search for the papers that have been published in Scopus, Google Scholar, JSTOR, and Semantic Scholar databases along with many websites. The researcher included the articles based on the scope, area, and variable, where biomedical and epidemiological research has been excluded. Findings: HR management is facing some invisible challenges that are not new, but during COVID-19, these were multiplied and reached the peaks. Employee health, safety, and mental well-being; employee maintenance, engagement, and flexibility; employee skill and talent management and motivation are the most common challenges.Practical Implications: The importance of this study lies in its implications on organizations to develop appropriate behavioral strategies to adapt the human resources to the new reality. HR practitioners can use the findings of this study to create effective interventions for dealing with their human resources in an uncertain situation like COVID-19.Originality/Value: The study presents multiple perspectives on the recent challenges that HR encounters. It is related to the behavioral implications of employees’ mental well-being and motivation for the HR professionals of the organizations.