Efficient characterization of wastewater stream quality is vital to ensure the safe discharge or reuse of treated wastewater (WW). There are numerous parameters employed to characterize water quality, some required by directives (e.g. biological oxygen demand (BOD), total nitrogen (TN), total phosphates (TP)), while others used for process controls (e.g. flow, temperature, pH). Well-accepted methods to assess these parameters have traditionally been laboratory-based, taking place either off-line or at-line, and presenting a significant delay between sampling and result. Alternative characterization methods can run in-line or on-line, generally being more cost-effective. Unfortunately, these methods are often not accepted when providing information to regulatory bodies. The current review aims to describe available laboratory-based approaches and compare them with innovative real-time (RT) solutions. Transitioning from laboratory-based to RT measurements means obtaining valuable process data, avoiding time delays, and the possibility to optimize the (WW) treatment management. A variety of sensor categories are examined to illustrate a general framework in which RT applications can replace longer conventional processes, with an eye toward potential drawbacks. A significant enhancement in the RT measurements can be achieved through the employment of advanced soft-sensing techniques and the Internet of Things (IoT), coupled with machine learning (ML) and artificial intelligence (AI).