The phosphodiesterase type 5 (PDE5) inhibitors, sildenafil, tadalafil and vardenafil, are a class of medications that are safe and effective in treating erectile dysfunction (ED). Yet, resuming sexual activity following a period of abstinence in response to ED may be anxiety-provoking for the man, his partner and their relationship, causing the sexual encounter to become a stressful event. The differences between PDE5 inhibitors in terms of duration of action can be successfully utilized by healthcare professionals to mitigate some of the psychosocial barriers that interfere with treating ED. PDE5 inhibitors with a longer duration of responsiveness provide some men with ED and their partners, a treatment option that may offer greater flexibility and potentially less anxiety surrounding the resumption of sexual activity. Shorter-acting PDE5s may be preferred by men/couples with predictable sexual scripts, excellent communication strategies and concerns regarding the duration of side effects.